Elucidation of Ligand/Protein Interactions between BCR-ABL Tyrosine Kinase and Some Commercial Anticancer Drugs Via DFT Methods

In this study, the interactions of 7 commercially available BCR-ABL tyrosine kinase enzyme inhibitors with amino acids in the active site of the relevant enzyme were investigated quantum mechanically. Here a per-residue study was carried out. Interaction energies were calculated by using the coordinates of the critical residues in the binding site of the enzyme and the drug molecules docked in this region. DFT methods were used during the QM processes. All interaction energies were calculated via M06-2X functional and 6-31G (d,p) basis set in vacuum. Based on the results obtained, it was tried to be determined which of the important residues in the binding cavity of the enzyme could better interact with the examined ligands. It is thought that this study may contribute to the development of tyrosine kinase enzyme inhibitors.

Investigation of discriminate and indiscriminate use of doxycycline in broiler: an indoor research on antibiotic doxycycline residue study in edible poultry tissue

Abuse of antibiotics is more common in developing countries including Bangladesh. The aim of this study was to detect doxycycline residue after discriminate and indiscriminate administration in broiler poultry. Eighteen broiler chicks, DOC (Cobb-500) was collected & reared up to 31 days. On day 16, they were randomly divided into 3 groups, namely group–A (Control group), group-B (Discriminate group) and group-C (Indiscriminate group). Each group contains 6 birds. The discriminate and indiscriminate groups were treated with antibiotic, doxycycline. In group-B withdrawal period was followed by treatment for 7 days. On the other hand, withdrawal period was not maintained in group-C, i.e. the antibiotic treatment was continued until the day of sacrifice. TLC analysis revealed that intensity of doxycycline in discriminate antibiotic group for liver, kidney, thigh muscle and breast muscle samples were found 63.33%, 65.33%, 22.67% and 26.00% respectively. And in indiscriminate antibiotic group intensity of doxycycline for liver, kidney, spleen, thigh muscle and breast muscle samples were found 50.67%, 50.33%, 39.50% and 48.17% respectively. All the samples of control group were found 0% intensity. The different among intensity were statistically significant. Overall, the present study documented the widespread abuse of doxycycline and failure to implement the recommended withdrawal period will undeniably leads to deposition of residues in broiler tissues. Asian J. Med. Biol. Res. March 2020, 6(1): 1-7

Germination Ecology of Two Australian Populations of African turnipweed (Sisymbrium thellungii)

African turnipweed (Sisymbrium thellungiiO. E.Schulz) is an emerging problematic broadleaf weed of the northern grain region of Australia. Laboratory experiments were conducted to evaluate the effects of temperature, light, salinity, pH, seed burial depth, and the amount of wheat crop residue on germination and emergence of two AustralianS. thellungiiweed populations (population C, cropped area; population F, fence line). Both populations behaved similarly across different environmental conditions, except in the residue study. Although the seeds of both populations ofS. thellungiicould germinate under complete darkness, germination was best (~95%) under light/dark conditions at the 20/10 C temperature regime. Both populations ofS. thellungiigerminated over a wide range of day/night temperatures (15/5, 20/10, 25/15, and 30/20 C). Osmotic stress had negative effects on germination, with 54% seeds (averaged over populations) able to germinate at −0.1MPa. Complete germination inhibition for both populations was observed at −0.8MPa osmotic potential. Both populations germinated at sodium chloride (NaCl) concentrations ranging from 50 to 100 mM, beyond which germination was completely inhibited. There were substantial reductions in seed germination, 32% (averaged over populations) under highly acidic conditions (pH 4.0) as compared with the control (water: pH 6.4). Seed germination of both populations on the soil surface was 77%, and no seedlings emerged from a burial depth of 1 cm. The addition of 6 Mg ha−1of wheat (Triticum aestivumL.) residue reduced the emergence of the C and F populations ofS. thellungiiby 75% and 64%, respectively, as compared with the control (no residue). Information gathered from this study provides a better understanding of the factors favorable for germination and emergence ofS. thellungii, which will aid in developing management strategies in winter crops, especially wheat, barley (Hordeum vulgareL.), and chick pea (Cicer arietinumL.).

Pharmacokinetics, tissue residues of tilmicosin phosphate (tilmicor-al®) and its in vitro and in vivo evaluation for the control of Mycoplas-ma gallisepticum infection in broiler chickens

The aim of present study was to determine the pharmacokinetics and tissue residues of tilmicosin phosphate (tilmicoral®) as well as its in vitro and in vivo evaluation for control of Mycoplasma gallisepticum (MG) infection in broiler chickens. Pharmacokinetics (single oral dose) and tissues residues (daily for five days) of tilmicosin (25 mg/kg b.wt) in broilers were investigated. Peak plasma concentration of tilmicosin was 1.25±0.0.09 μg/mL and achieved at 3.15±0.34 h. Elimination half-life was long (44.3±7.22 h) and Vdarea was large (1.25±0.082 L/kg). Residue study revealed a good distribution and penetration of tilmicosine in lung, liver, kidney and muscles. Tilmicosin could not be detected in all tested tissues (except in lung) at 6 days after last administration. The MIC of tilmicosin and tylosin against MG were 0.054 and 0.319 μg/mL, respectively. MG infected chickens and treated by tilmicosin or tylosin showed a significant (p<0.05) improvement in mean body weights gain and a significant (p<0.05) decline in mean clinical signs score, air sac lesion score and mortality rate, however tilmicosin was a superior drug. In conclusion, timicoral® was a very effective medication for controlling MG infection in broiler chickens due to its rapid absorption, long elimination half-life, rapid and extensive penetration from blood into tissues especially lungs and air sacs. Additionally, tilmicoral® had a short withdrawal time. Moreover, its superior efficacy (in vitro and in vivo) against MG.